Direct comparisons of different drugs used for the same indication can reveal important differences in efficacy or tolerability. Such clinical differences can often be explained or predicted on the basis of the particular pharmacological properties of each drug. To demonstrate the clinical importance of understanding the distinct pharmacology of a drug, this article describes the pharmacology and clinical profile of mirtazapine (Remeron). Mirtazapine is a pharmacologically unique agent among antidepressant drugs. Clinical studies have demonstrated similar overall efficacy for mirtazapine compared with the serotonin reuptake inhibitors and with venlafaxine (Effexor), but a more rapid onset of antidepressant effect and a substantially different side effect profile. Knowledge about drug pharmacology leads to better understanding of the differences in the efficacy and tolerability of various drugs. This knowledge also provides a rationale for choosing one drug over another for a particular patient or switching or combining drugs for treating nonresponders or alleviating side effects.